title: c-Abl Kinase Is a Regulator of αvβ3 Integrin Mediated Melanoma A375 Cell Migration.
abstract: Integrins are heterodimeric transmembrane receptors that physically link the extracellular matrix (ECM) to the intracellular actin cytoskeleton, and are also signaling molecules that transduce signals bi-directionally across the plasma membrane. Integrin regulation is essential for tumor cell migration in response to growth factors. c-Abl kinase is a nonreceptor tyrosine kinase and is critical for signaling transduction from various receptors. Here we show that c-Abl kinase is involved in A375 cell migration mediated by αvβ3 integrin in response to PDGF stimulation. c-Abl kinase colocalizes with αvβ3 integrin dynamically and affects αvβ3 integrin affinity by regulating its cluster. The interaction between c-Abl kinase and αvβ3 integrin was dependent on the activity of c-Abl kinase induced by PDGF stimulation, but was not dependent on the binding of αvβ3 integrin with its ligands, suggesting that c-Abl kinase is not involved in the outside-in signaling of αvβ3 integrin. Talin head domain was required for the interaction between c-Abl kinase and αvβ3 integrin, and the SH3 domain of c-Abl kinase was involved in its interaction with talin and αvβ3 integrin. Taken together, we have uncovered a novel and critical role of c-Abl kinase in αvβ3 integrin mediated melanoma cell migration.
authors.affiliation: Department of Cell Biology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin Province, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.forename: Ruifei
authors.initials: R
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.forename: Khamal Kwesi
authors.initials: KK
authors.lastname: Ampah
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Wang
authors.forename: Xianlu
authors.initials: X
authors.lastname: Zeng
mesh_terms: D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016608:Talin / Q000378:metabolism
chemical_list: D000199:Actins; D039302:Integrin alphaVbeta3; D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D016608:Talin; D016315:Proto-Oncogene Proteins c-abl